Purchase this article with an account.
S. Sugita, Y. Futagami, S. Horie, M. Mochizuki, T.F. Ng, J.W. Streilein; Iris Pigment Epithelium (IPE) and IPE Regulatory T Cells Suppress Activation of T Cells via Membrane–Bound TGF–Beta . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5134.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To examine whether iris PE (IPE) and the regulatory T cells co–cultured with IPE (IPE Tregs) suppress T cell activation via TGFb/TGFb receptor interactions.
Primary cultured IPE cells were established from normal C57BL/6 mice. T cells were co–cultured with IPE, x–irradiated, and used as regulators (IPE Tregs). Target bystander T cells were established from normal splenic T cells with anti–CD3 antibodies. T–cell activation was assessed for proliferation by [3H]–thymidine incorporation. Neutralization with anti–TGFb antibodies or T cells from dominant negative TGFb RII mice were used to abolish regulatory function. Expression of TGFb and the receptors (TGFb RI and RII) on IPE and IPE–exposed CD8+ T cells was evaluated with oligonucleotide microarray, RT–PCR, immune staining and flow cytometry. CD8+ IPE Tregs were depleted of membrane–bound TGFb+ T cells and assayed for suppressive activity by adding them to bystander T cells.
Naïve CD8+ T cells acquired T regulatory activity when exposed to IPE in vitro. In the conversion, IPE and responding T cells must express membrane–bound TGFb. IPE produced both soluble and membrane bound active TGFb, but only the latter was actually delivered to CD8+ T cells. In turn, these T cells became IPE Tregs by up–regulating their own expression of B7 co–stimulatory molecules and soluble and membrane–bound TGFb. IPE Tregs through their expression of B7 were able to engage CTLA–4+ bystander T cells, which enabled the precise, targeted delivery of membrane–bound TGFb.
IPE promote conversion of T cells into Tregs solely through a contact–dependent mechanism by membrane–bound TGFb and co–stimulatory molecules. CD8+ T cells exposed to IPE acquire full regulatory capacity.
This PDF is available to Subscribers Only